Fanconi Anemia Patients from an Indigenous Community in Mexico Carry a New Founder Pathogenic Variant in FANCG

Fanconi anemia (FA) is a rare genetic disorder caused by pathogenic variants (PV) in at least 22 genes, which cooperate in the FA/BRCA pathway to maintain genome stability. PV in FANCA, FANCC, and FANCG account for most cases (~90%). This study evaluated the chromosomal, molecular, and phenotypic findings of a novel founder FANCG PV, identified in three patients with FA from the Mixe community of Oaxaca, Mexico. All patients presented chromosomal instability and a homozygous PV, FANCG: c.511-3_511-2delCA, identified by next-generation sequencing analysis. Bioinformatics predictions suggest that this deletion disrupts a splice acceptor site promoting the exon 5 skipping. Analysis of Cytoscan 750K arrays for haplotyping and global ancestry supported the Mexican origin and founder effect of the variant, reaffirming the high frequency of founder PV in FANCG. The degree of bone marrow failure and physical findings (described through the acronyms VACTERL-H and PHENOS) were used to depict the phenotype of the patients. Despite having a similar frequency of chromosomal aberrations and genetic constitution, the phenotype showed a wide spectrum of severity. The identification of a founder PV could help for a systematic and accurate genetic screening of patients with FA suspicion in this population.

Integrating Wheat Nucleolus Structure and Function: Variation in the Wheat Ribosomal RNA and Protein Genes

We review the coordinated production and integration of the RNA (ribosomal RNA, rRNA) and protein (ribosomal protein, RP) components of wheat cytoplasmic ribosomes in response to changes in genetic constitution, biotic and abiotic stresses. The components examined are highly conserved and identified with reference to model systems such as human, Arabidopsis, and rice, but have sufficient levels of differences in their DNA and amino acid sequences to form fingerprints or gene haplotypes that provide new markers to associate with phenotype variation. Specifically, it is argued that populations of ribosomes within a cell can comprise distinct complements of rRNA and RPs to form units with unique functionalities. The unique functionalities of ribosome populations within a cell can become central in situations of stress where they may preferentially translate mRNAs coding for proteins better suited to contributing to survival of the cell. In model systems where this concept has been developed, the engagement of initiation factors and elongation factors to account for variation in the translation machinery of the cell in response to stresses provided the precedents. The polyploid nature of wheat adds extra variation at each step of the synthesis and assembly of the rRNAs and RPs which can, as a result, potentially enhance its response to changing environments and disease threats.

AYURVEDIC UNDERSTANDING & PREVENTIVE MEASURES OF COVID-19: AN OVERVIEW

The world community is facing a pandemic of COVID -19, which is caused by infection of novel corona virus-2. The disease has spread globally with a total of 27.2 Cr conrmed cases, 53.3 L deaths and 24.3 Cr recovered as of December 13. Primarily; it involves the respiratory system and in due course of time affects the other systems too. The pathophysiology and management are still evolving in modern medicine, while developments of vaccine are under the way. As per Ayurveda, it is type of Aupasargikaroga (infectious disease) that is Sankramakaroga (communicable disease) in nature and later on it may derange the basic matrix of bio-humours and alter the status of Agnis (bio-res) and Ojas (immune strength). In view of this, different treatments guidelines have been recommended in the classics of Ayurveda by considering the genetic constitution (Prakriti), kala, bala and other epigenetic factors of the patient. Besides, specic recommendations for Ahara (diet), Nidra (sleep) and Brahmacharya (code of conduct related to mental and physical activities) have also been mentioned to target physical, mental, social and spiritual health. In this context authors have tried to explore the preventive aspects which are feasible for general public to become free from COVID-19 through Ayurveda.

Molecular Characterization of Fungi Associated with Dump Site Soil

Aims: A study was conducted to identify fungal species isolated from dumpsite soil in University of Port Harcourt using molecular techniques. Methodology: Molecular methods for determining the species of a fungus based on the amplification and sequencing of the internal subscribed spacer (ITS) region of the fungal rRNA operon using molecular markers was applied. Soil sample was collected from a dumpsite in the University of Port Harcourt, Rivers State, Nigeria. Isolation of fungi associated with the dumpsite soil was carried out using spread plate method. Fungal genomic DNA was extracted using Quick-DNA Fungal/Bacterial Miniprep kit. The ITS1-2 gene of the isolates was amplified by Polymerase Chain Reaction (PCR) using the primer pair; ITS4 and ITS5. Results: The sequences of the amplified ITS region were blasted against known sequences on the National Centre for Biotechnology Information (NCBI) database. Nucleotide sequence analysis revealed the species identity of the fungal isolates to be: Aspergillus fumigatus, Trichoderma harzianum, Aspergillus felis, Aspergillus templicola, Aspergillus flavipes, Aspergillus fumigatus and Cunninghamella binariae. Phylogenetic analysis was carried out to ascertain the relationship between the isolates and other closely-related isolates on GenBank. Isolates 2 (Trichoderma harzianum) and 7 (Cunninghamella binariae), 3 (Aspergillus felis) and 6 (Aspergillus fumigatus), and 4 (Aspergillus templicola) and 5 (Aspergillus flavipes) were found to be more closely related to each other. Conclusion: The molecular techniques employed successfully identified the organisms to the species level as these techniques are based on the genetic constitution of organisms. The result obtained from this study will complement the information on the fungal organisms associated with dumpsite soil.

Evaluation and genetic analysis of common bean genotypes (Phaseolus vulgaris L.) at Dibatie and Mandura, Northwestern Ethiopia

Assessing and understanding the variations existing in crops due to genetic composition and environmental variability is very important in order to exploit the genetic constitution of crop plants. To this aim, variability measures such as phenotypic coefficient of variation (PCV) and genotypic coefficient of variation (GCV) are commonly used. Heritability and genetic advance are major concerns for common bean to identify important traits for common bean genetic improvement. The field experiment was conducted at Mandura and Dibatie research substations working with sixteen genotypes of the common bean during 2017/2018 in lattice design with three replications to evaluate the performance of common bean genotypes and estimate the genetic variability. Heritability and genetic advance were estimated in relation to yield and its component traits for future breeding programs. Combined analysis of variance across locations revealed highly significant variations among genotypes for all traits under study. The PCV ranged from 3.36% for days to flowering to 15.91% for a number of pods per plant while the GCV value ranged from 0.75% for days to flowering to 13.74% for the number of pods per plant. Broad sense heritability values ranged from 5.00% for days to flowering to 84.61% for a hundred seed weight. Generally, the result of the study showed that significant genetic variability among tested genotypes and a simple selection for effective improvement of these traits. Keywords: common bean, genetic variability, genetic advance, heritability

Cancer: More Than a Geneticist’s Pandora’s Box

Despite identical genetic constitution, a cancer cell population can exhibit phenotypic variations termed as non-genetic/non-mutational heterogeneity. Such heterogeneity – a ubiquitous nature of biological systems – has been implicated in metastasis, therapy resistance and tumour relapse. Here, we review the evidence for existence, sources and implications of non-genetic heterogeneity in multiple cancer types. Stochasticity/ noise in transcription, protein conformation and/or external microenvironment can underlie such heterogeneity. Moreover, the existence of multiple possible cell states (phenotypes) as a consequence of the emergent dynamics of gene regulatory networks may enable reversible cell-state transitions (phenotypic plasticity) that can facilitate adaptive drug resistance and higher metastatic fitness. Finally, we highlight how computational and mathematical models can drive a better understanding of non-genetic heterogeneity and how a systems-level approach integrating mathematical modelling and in vitro/in vivo experiments can map the diverse phenotypic repertoire, and identify therapeutic vulnerabilities of an otherwise clonal cell population.

Securing genetic integrity in freshwater pearl mussel propagation and captive breeding

Securing genetic integrity is of key importance in conservation-oriented captive breeding programs releasing juveniles into the wild. This is particularly true for species such as the endangered freshwater pearl mussel (Margaritifera margaritifera) for which a number of captive breeding facilities has been established in Europe. The core objective of this study was to compare the genetic constitution of 29 cohorts of captive-bred freshwater pearl mussels from five different breeding facilities in Austria, France, Luxembourg and Germany, with their original 14 source populations from nine major European drainages, based on microsatellite markers. Captive-bred mussels represented 11 different genetic clusters, suggesting an important contribution of the breeding stations to securing the genetic diversity of the species. In almost all cases, the cultured offspring closely resembled the genetic constitution of the source mussels as revealed from the STRUCTURE analysis and the generally high assignment of offspring to the original source populations. The majority of captive-bred cohorts had an increased inbreeding coefficient and decreased genetic variability compared to their source populations as measured by AR and HO. Highest numbers of deformed juveniles coincided with very low levels of HO < 0.05. Since erosion of genetic diversity in captive breeding was mostly evident in individual year-cohorts, long-term breeding over multiple years can minimize such effects. The systematic selection of priority populations for conservation, effective breeding strategies avoiding effects of in- and outbreeding by genetically informed selection of parent individuals, and a network of collaboration among the different breeding facilities would be very useful to increase resilience and effectiveness.

Distribution of Human-specific Alu InDel Polymorphisms in the Brahmin and Rajput Populations of Kangra District of Himachal Pradesh, North India

ABSTRACT The genetic constitution of two endogamous caste populations viz., the Brahmin (n=250) and Rajput (n=250) of Kangra district of the North Indian state of Himachal Pradesh was studied using six autosomal Alu InDel (insertion/deletion) markers viz., ACE, APO, PV92, CD4, PLAT, and TPA25 All markers were found to be polymorphic. Except for Alu APO and PV92 in the Rajput, genotype frequencies of other markers were in the Hardy-Weinberg equilibrium in both the populations. The average heterozygosity (H) was observed higher in the Brahmin (0.4134) compared to the Rajput (0.3809) and the degree of genic differentiation was low between them (GST =0.00898). The genetic distance analysis revealed close genetic affinities of the present Rajput population with the Gaddi Rajput and Gaddi Brahmin populations reported earlier from the district but the present Brahmin population was found distant from them.

Dose–Response Relationships between Levels of Alcohol Use and Risks of Mortality or Disease, for All People, by Age, Sex and Specific Risk Factors

Alcohol use has been causally linked to more than 200 disease and injury conditions, as defined by three-digit ICD-10 codes. The understanding of how alcohol use is related to these conditions is essential to public health and policy research. Accordingly, this study presents a narrative review of different dose–response relationships for alcohol use. Relative-risk (RR) functions were obtained from various comparative risk assessments. Two main dimensions of alcohol consumption are used to assess disease and injury risk: (1) volume of consumption, and (2) patterns of drinking, operationalized via frequency of heavy drinking occasions. Lifetime abstention was used as the reference group. Most dose–response relationships between alcohol and outcomes are monotonic, but for diabetes type 2 and ischemic diseases, there are indications of a curvilinear relationship, where light to moderate drinking is associated with lower risk compared with not drinking (i.e., RR < 1). In general, women experience a greater increase in RR per gram of alcohol consumed than men. The RR per gram of alcohol consumed was lower for people of older ages. RRs indicated that alcohol use may interact synergistically with other risk factors, in particular with socioeconomic status and other behavioural risk factors, such as smoking, obesity, or physical inactivity. The literature on the impact of genetic constitution on dose–response curves is underdeveloped, but certain genetic variants are linked to an increased RR per gram of alcohol consumed for some diseases. When developing alcohol policy measures, including low-risk drinking guidelines, dose–response relationships must be taken into consideration.

Genetic diversity and population structure analysis of Lateolabrax maculatus from Chinese coastal waters using polymorphic microsatellite markers

In order to provide valuable guidelines for the conservation of germplasm of Lateolabrax maculatus, the genetic diversity and population structure analysis were evaluated for eight geographic populations along coastal regions of China, using 11 microsatellite DNA markers. The genetic parameters obtained showed that, eight populations can be clustered into two groups, the Northern group and the Southern group, concordant with their geographical positions. The UPGMA tree constructed according to the Nei’s genetic distance along with the structure analysis and discriminant analysis of principal component also supported this result. This might be explained by the geographic separation and the divergent environmental conditions among the populations. It's worth noting that, QD (Qingdao) population from northern area was assigned to the Southern group and showed a close genetic relationship and similar genetic constitution with the southern populations. We speculated that large scales of anthropogenic transportation of wild fries from QD populations to the southern aquaculture areas in history should be the primary cause. The populations from GY (Ganyu), RD (Rudong) and BH (Binhai) had higher genetic diversity and showed limited genetic exchange with other populations, indicating better conservation of the natural resources in these regions. All populations were indicated to have experienced bottleneck events in history.